rs3814316

Variant names:

• chr1-155177242-G-A
• rs3814316
• NM_025058.5:c.861G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-155177242-G-A
• chr1-155177242-G-C
• chr1-155177242-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_025058.5(TRIM46):​c.861G>A​(p.Thr287Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,613,686 control chromosomes in the GnomAD database, including 127,443 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11219 hom., cov: 32)
  • Exomes 𝑓: 0.39 (116224 hom.)
• Consequence: TRIM46 NM_025058.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 42 publications found

Genes affected

TRIM46 (HGNC:19019): (tripartite motif containing 46) This gene encodes a protein of the tripartite motif (TRIM) family. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. TRIM46 is reported to be involved in the proliferation of multiple types of cancer cells including lung and breast cancer. It has also been shown to control neuronal polarity and axon specification by forming uniform microtubule bundles in the axon. [provided by RefSeq, May 2022]

ENSG00000273088 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM46	NM_025058.5	c.861G>A	p.Thr287Thr	synonymous_variant	Exon 5 of 10	ENST00000334634.9	NP_079334.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM46	ENST00000334634.9	c.861G>A	p.Thr287Thr	synonymous_variant	Exon 5 of 10	1	NM_025058.5	ENSP00000334657.4
ENSG00000273088	ENST00000473363.3	c.49-3768C>T		intron_variant	Intron 1 of 4	5		ENSP00000477381.3

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56193 AN: 151906 Hom.: 11221 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.367

GnomAD2 exomes AF: 0.433 AC: 108881 AN: 251372 AF XY: 0.424

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.765

Gnomad FIN exome AF: 0.460

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.405

GnomAD4 exome AF: 0.387 AC: 565986 AN: 1461660 Hom.: 116224 Cov.: 47 AF XY: 0.386 AC XY: 280778 AN XY: 727138

African (AFR) AF: 0.263 AC: 8796 AN: 33478

American (AMR) AF: 0.590 AC: 26377 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 7346 AN: 26136

East Asian (EAS) AF: 0.799 AC: 31704 AN: 39698

South Asian (SAS) AF: 0.440 AC: 37939 AN: 86240

European-Finnish (FIN) AF: 0.459 AC: 24490 AN: 53408

Middle Eastern (MID) AF: 0.267 AC: 1538 AN: 5768

European-Non Finnish (NFE) AF: 0.364 AC: 404714 AN: 1111818

Other (OTH) AF: 0.382 AC: 23082 AN: 60390

GnomAD4 genome AF: 0.370 AC: 56200 AN: 152026 Hom.: 11219 Cov.: 32 AF XY: 0.379 AC XY: 28124 AN XY: 74298

African (AFR) AF: 0.273 AC: 11309 AN: 41492

American (AMR) AF: 0.486 AC: 7428 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 962 AN: 3468

East Asian (EAS) AF: 0.770 AC: 3957 AN: 5136

South Asian (SAS) AF: 0.438 AC: 2111 AN: 4824

European-Finnish (FIN) AF: 0.456 AC: 4821 AN: 10568

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24503 AN: 67952

Other (OTH) AF: 0.361 AC: 761 AN: 2108

Alfa AF: 0.364 Hom.: 48027

Bravo AF: 0.374

Asia WGS AF: 0.544 AC: 1890 AN: 3478

EpiCase AF: 0.326

EpiControl AF: 0.329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.94
DANN	Benign	0.81
PhyloP100		-1.6
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3814316; hg19: chr1-155149718; COSMIC: COSV55280507; COSMIC: COSV55280507;